1. Field of the Invention
The present invention relates to a tandem time-of-flight mass spectrometer used in quantitative analysis and simultaneous qualitative analysis of trace compounds and also in structural analysis of sample ions. The invention also relates to a method of mass spectrometry using this tandem-of-flight mass spectrometer.
2. Description of Related Art
[Time-of-Flight Mass Spectrometer (TOFMS)]
A time-of-flight (TOF) mass spectrometer is an instrument that finds the mass-to-charge ratio (m/z) of each ion by accelerating ions with a given accelerating voltage, causing them to fly, and calculating the m/z from the time taken for each ion to reach a detector. In TOFMS, ions are accelerated by a given pulsed voltage Va. At this time, the velocity of the ion, v, is found from the law of conservation of energy and given by
                                          mv            2                    2                =                  qeV          a                                    (        1        )                                v        =                                            2              ⁢                              qeV                a                                      m                                              (        2        )            where m is the mass of the ion, q is the electric charge of the ion, and e is the elementary charge.
Therefore, the flight time T required for the ion to reach a detector, placed behind at a given distance of L, is given by
                    T        =                              L            v                    =                      L            ⁢                                          m                                  2                  ⁢                                      qeV                    a                                                                                                          (        3        )            
As can be seen from Eq. (3), TOFMS is an instrument that separates masses by employing the fact that the flight time T differs according to the mass m of each ion. One example of the linear TOFMS is shown in FIG. 1. Reflectron TOFMS that permits improvement of the energy convergence and elongation of flight time by placing a reflectron field between an ion source and a detector has enjoyed wide acceptance. One example of the reflectron TOFMS is shown in FIG. 2.
[Improvement of Performance of TOFMS]
The mass resolution of a TOF mass spectrometer is defined as follows:
                              mass          ⁢                                          ⁢          resolution                =                  T                      2            ⁢            Δ            ⁢                                                  ⁢            T                                              (        4        )            where T is the total flight time and ΔT is a peak width.
That is, if the peak width ΔT is made constant and the total flight time T can be lengthened, the mass resolution can be improved. However, in the related art linear or reflectron type TOFMS, increasing the total flight time T (i.e., increasing the total flight distance) will lead directly to an increase in instrumental size. A multi-pass time-of-flight mass spectrometer has been developed to realize high mass resolution while avoiding an increase in instrumental size (see M. Toyoda, D. Okumura, M Ishihara and I. Katakuse, J. Mass Spectrom., 2003, 38, pp. 1125-1142). This instrument uses four toroidal electric fields each consisting of a combination of a cylindrical electric field and a Matsuda plate. The total flight time T can be lengthened by accomplishing multiple turns in an 8-shaped circulating orbit. In this apparatus, the spatial and temporal spread at the detection surface has been successfully converged up to the first-order term using the initial position, initial angle, and initial kinetic energy.
However, the TOFMS in which ions revolve many times in a closed trajectory suffers from the problem of overtaking. That is, because ions revolve multiple times in a closed trajectory, lighter ions moving at higher speeds overtake heavier ions moving at smaller speeds. Consequently, the fundamental concept of TOFMS that ions arrive at the detection surface in turn first from the lightest one does not hold.
The spiral-trajectory TOFMS has been devised to solve this problem. The spiral-trajectory TOFMS is characterized in that the starting and ending points of a closed trajectory are shifted from the closed trajectory plane in the vertical direction. To achieve this, in one method, ions are made to impinge obliquely from the beginning (see JP-A-2000-243345). In another method, the starting and ending points of the closed trajectory are shifted in the vertical direction using a deflector (see JP-A-2003-86129). In a further method, laminated toroidal electric fields are used (see JP-A-2006-12782).
Another TOFMS has been devised which is based on a similar concept but in which the trajectory of the multi-pass TOF-MS (see GB2080021) where overtaking occurs is zigzagged (see WO2005/001878 pamphlet).
[MS/MS Measurements and TOF/TOF Instrumentation]
In mass spectrometry, ions generated by an ion source are separated according to m/z value by a mass analyzer and detected. The results are represented in form of a mass spectrum in which m/z values and relative intensities of ions are graphed. This measurement is hereinafter referred to as an MS measurement, in contrast with MS/MS measurements. In an MS/MS measurement (see FIG. 3), certain ions generated by an ion source are selected as precursor ions by a first stage of mass spectrometer (MS1), are made to fragment spontaneously or forcibly to thereby produce product ions, and the product ions are mass analyzed by a second stage of mass spectrometer (MS2). An instrument enabling an MS/MS measurement is referred to as an MS/MS instrument (see FIG. 4). In the MS/MS measurement shown in FIG. 3, the m/z values of the precursor ions, the m/z values of the product ions generated in plural fragmentation paths, and their relative intensity information are obtained and, therefore, it is possible to perform structural analysis of the precursor ions.
MS/MS equipment where two TOFMS instruments are connected in series is generally known as a tandem TOF (or TOF/TOF) instrument. This is mainly used in a system using a MALDI ion source. Many conventional, tandem TOF spectrometers are composed of a linear TOFMS and a reflectron TOFMS (see FIG. 5). An ion gate is placed between the two TOFMS instruments to select precursor ions. The focal point of the first TOFMS instrument is placed near the ion gate. In some cases, precursor ions fragment spontaneously. In other cases, precursor ions are forced to fragment in a collision cell placed ahead of a reflectron field produced either by the first TOFMS instrument or the second TOFMS instrument.
A method of selecting plural precursor ions in a single flight time measurement (see WO2005/001878 pamphlet) that is especially associated with the present invention is described. Where the second TOFMS instrument has a longer flight time than the first TOFMS instrument as encountered where the first and second TOFMS instruments are made of a linear TOFMS and a reflectron TOFMS, respectively, it is only possible to perform an MS/MS measurement where only one precursor ion is selected for measurement using a single flight time.
At this time, it follows that ions, other than the selected precursor ions, waste the sample. However, where the first TOFMS instrument provides a sufficiently longer flight time than the second TOFMS instrument, plural precursor ions can be selected in a measurement using a single flight time. Where the value obtained by dividing the flight time through the first TOFMS by the flight time through the second TOFMS is 0.5, 2, 5, and 10, respectively, the relationship between the mass of the initially selected precursor ions and the mass of precursor ions that can be selected next is illustrated in the table of FIG. 6.
As is obvious from FIG. 6, as the difference of the flight time through the first TOFMS instrument with the flight time through the second TOFMS instrument increases, more precursor ions can be selected during a measurement using a single flight time. It is seen that the utilization efficiency of the sample is enhanced greatly compared with the case where only one precursor ion can be selected.
One method of elongating the flight time through the first TOFMS instrument is to set the accelerating voltage for the first TOFMS instrument much smaller than the accelerating voltage for the second TOFMS instrument. Another method is to adopt a TOFMS instrument having a long flight time as the first TOFMS instrument. In either method, however, the transmittance of precursor ions through the first TOFMS instrument deteriorates because of an increase in the flight time. If the first TOFMS instrument is made too long, the attenuation of ion amount passed through the first TOFMS relative to the ion amount of precursor ions generated in the ion source can no longer be neglected.
One problem with the related art tandem TOF mass spectrometry is that, in a case where the flight time through the first TOFMS instrument is shorter than the flight time through the second TOFMS instrument, only one precursor ion can be selected during a measurement using a single flight time. This leads to sample wastage. In a case where the flight time through the first TOFMS instrument is sufficiently greater than (e.g., more than 10 times) the flight time through the second TOFMS instrument, plural precursor ions can be selected during a measurement of a single flight time but the transmittance of the ions through the first TOFMS instrument deteriorates. This also leads to a decrease in the sample utilization efficiency.